Ion cyclotron resonance mass spectrometry (ICR-MS) involves exciting ions at their ion cyclotron resonance (ICR) frequency and then observing the transient decay of the image currents induced on detection plates located adjacent the resonating ions. The electrical signals from the detection plates may be Fourier-transformed to produce frequency or mass spectrum data. Ion cyclotron resonance mass spectrometry that involves such Fourier transformations may also be referred to as Fourier-transform ion cyclotron resonance mass spectrometry, “FT-ICR-MS,” “FTICR,” or simply “FTMS.”
Fourier transform ion cyclotron resonance mass spectrometry differs from other mass spectrometry techniques in that the ions are not detected by hitting a detector, but only by passing near detection plates. Additionally, the ion masses are not resolved in space or in time as with other techniques, but only in frequency. Stated another way, the different ions are not detected in different places as with sector instruments or at different times as with time-of-flight instruments.
A typical FTICR spectrometer involves a cube-shaped container or “cell” having three opposed sets of plates arranged to form the cube shape. The plates comprising the cell are positioned in a uniform magnetic field so that one pair of plates is orthogonal to the magnetic field, whereas the other two pairs of plates are generally parallel to the magnetic field. The three sets of plates are electrically connected to a voltage source that is operable to place various voltages on the plates to achieve various operational modes for the cell. The pair of plates that is orthogonal to the magnetic field is often referred to as the trapping plates. One of the other sets of opposed plates, commonly referred to as the excitation plates, is used to excite the ions, whereas the other opposed set of plates, commonly referred to as the detection plates, is used to detect the resonating ions.
In operation, a trapping voltage is placed on the trapping plates, creating an electric field within the cell. The combination of the electric and magnetic fields confine or trap the ions within the cell. Generally speaking, the ions are radially confined by the magnetic field and axially confined by the electric field. The ions oscillate between the trapping plates at a so-called z-axis trapping frequency, as the Cartesian z-axis is often selected as the axis that passes through the trapping plates. The electric and magnetic fields induce three general motions on the ions trapped within the cell: cyclotron motion, trapping motion, and magnetron motion. The magnetic field causes the ions to have a cyclotron frequency that is inversely proportional to their mass-to-charge (m/z) ratio. That is, ions with smaller m/z ratios will have higher cyclotron frequencies, whereas those with larger m/z ratios will have lower cyclotron frequencies. The ions trapped within the cell may be produced within the cell itself (e.g., by any of a wide range of ionization techniques), or may be produced external to the cell, then introduced into the cell by appropriate means.
Once a suitable number of ions is trapped within the cell, the cell may be switched to an excitation mode of operation, in which the ions are excited while remaining trapped within the cell. In the excitation mode of operation, an excitation signal (e.g., an alternating signal in the radio-frequency (RF) range) is applied on the two excitation plates. Generally speaking, the RF signals applied to the opposing excitation plates are 180° out of phase relative to each other. Because the excitation electric field is applied in addition to the trapping field, the ions will remain trapped within the cell (i.e., the ions are still subject to the trapping field), even as they are excited or energized due to the application of the excitation electric field. The RF excitation signal can be applied as a discrete frequency, as multiple discrete frequencies, or as a “chirp” in which the frequency is swept through a defined range of amplitudes and frequencies. Just as a tuning fork of the same frequency can gain energy from a similar tuning fork vibrating in a room, the ions trapped within the cell gain energy when the frequency of the voltage on the excitation plates is the same as the ion resonance cyclotron frequency. The increased energy of the ions causes the radii of the ion orbits to increase while the cyclotron frequency of the ions remains the same.
After the excitation event, the resonating ions of equivalent mass-to-charge (m/z) ratio are substantially in phase (i.e., coherent) and at sufficiently large orbits (i.e., their cyclotron radii have increased even though their cyclotron frequencies remain the same) that they can be detected by the detection plates. If the ions are positively charged, they attract electrons in the detection plates as they pass by, thus inducing a signal. If the ions are negatively charged, they repel the electrons in the detection plates. The signal between the two opposed detection plates has the same frequency as the cyclotron frequency of the resonating ions. The signal may then be amplified, digitized, and Fourier-transformed into mass spectrum data.
More recently, FTICR mass spectrometers have been developed wherein the cell takes the form of a Penning trap. Briefly, a Penning trap is a device that utilizes a linear magnetic field and a quadrupole electric field to confine ions or other charged particles within the trap. The quadrupole electric field may be generated by using a set of three electrodes, a ring and two end cap electrodes, for example. The ring and end cap electrodes are typically hyperboloids of revolution so that the electric field created between the electrodes has the desired quadrupole shape.
In theory, the effective cyclotron frequency of an ion trapped within the FTICR mass spectrometer will be independent of the position of the ion within the spectrometer as well as its cyclotron radius. According to the literature, the desired field within an FTICR is a quadrupole field. Unfortunately, however, this effect is only approached near the center or “saddle” of the quadrupole field. Ions located away from the center or saddle of the field are subject to various non-linearities that adversely affect their behaviors and the resulting data. For example, the trapping electric field produced by the end cap electrodes tends to shield or insulate ions located near the end cap electrodes from the excitation field. Consequently, ions located near the end cap electrodes are not excited to the same degree as ions located elsewhere. The shielding effect also makes it more difficult to detect excited ions near the end cap electrodes. The problem is made worse by the fact that the ions spend a substantial portion of time near the end cap electrodes, i.e., where the excitation and detection processes are least efficient.
Still other problems arise from the fact that most of the quadrupole field lines are not parallel to the magnetic field lines. The non-parallel fields induce magnetron effects on the ions, which are detrimental. For example, induced magnetron effects in cells utilizing a quadrupole field decrease the cyclotron frequency of the ions. While it is possible to correct the reduced cyclotron frequency (e.g., via calibration), the induced magnetron effects also lead to a loss of ion cloud coherence, which results in reduced resolution. An excessive number of ions are also lost to the cell in such systems, which limits resolution and detection limits. The induced magnetron effects, as well as non-linearities in the excitation and detection of the ions, also limits the effective mass-to-charge ratio range that can be observed for a given set of operational parameters. Consequently, Fourier transform ion cyclotron resonance spectroscopy systems have failed to realize their full potential.